Project 1 Abstract The burden of age-related dementias, including Alzheimer?s disease and related dementias (ADRD), remains understudied in much of Africa, with a few notable exceptions.1-4 By 2040, an estimated 70% of the 80 million people with dementia globally will reside in low and middle income countries.5 Dementia is a particular issue for these countries, such as South Africa, where life expectancies are expected to rise dramatically.6-9 7-9 Within virtually all countries, cognitive decline has shown strong disparities with household income and educational attainment.10, 11 South Africa is no exception and the associations with low levels of education and lifelong disadvantage are substantial. Our long-term goal is to understand the epidemiologic patterns and projected public health burden of ADRD in South Africa, as well as to identify factors that either reduce or increase ADRD risk. With this renewal application for the Health and Aging in Africa: Longitudinal Studies of an INDEPTH Community (HAALSI) Program, we propose to take a major step towards this goal by conducting longitudinal cognitive and dementia-related assessments in HAALSI , a population-based community cohort of adults ?40 years of age. Project 1 is integrated with Projects 2 (Cardiometabolic Disease) and 3 (HIV) to optimize goals. We have cognitive measures harmonized with the Health and Retirement Study and sister studies for the HAALSI cohort of 5,059 adults ?40 years of age. We propose the following aims: AIM 1: Obtain information on the incidence and prevalence of ADRD as well as mild cognitive impairment (MCI). By year 05, we will have three cognitive assessments over three waves with six years of longitudinal information on cognitive function, mortality follow-up and clinical and informant assessments. These data will permit us to (1A) identify rates of all-cause dementia and MCI; and (1B) evaluate impacts of vascular conditions and HIV on all-cause dementia and MCI and calculate attributable risk. To accomplish this, we will use information from our neuropsychological batteries, clinical examination, and biomarkers of risk related to HIV, antiretroviral therapy (ART), and vascular disorders. AIM 2: Identify social and economic risk and resilience factors affecting cognitive decline and ADRD. We hypothesize that educational attainment and social networks help older adults maintain high cognitive functioning as they age (cognitive reserve).12-16 We determine whether social engagement drawn from network structures protects against decline.12, 17-24 We examine moderating conditions related to gender and age. AIM 3: Evaluate associations of Apoliprotein E (APOE) and markers of biological aging related to telomeres with cognitive decline and ADRD. In a subsample of 2,000 we will investigate the role of these genetic markers and ADRD and identify risks and interactions with educational attainment and ADRD.